1. Field of the Invention
The present invention relates to novel galectins. More specifically, isolated nucleic acid molecules are provided encoding human galectin 8, 9, 10, or 10SV. Galectin 8, 9, 10 and 10SV polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of galectin 8, 9, 10, or 10SV activity. Also provided are diagnostic methods for detecting cell growth disorders and therapeutic methods for cell growth disorders, including autoimmune diseases, cancer, and inflammatory diseases.
2. Related Art
Lectins are proteins that bind to specific carbohydrate structures and can thus recognize particular glycoconjugates. Barondes et al., J. Biol. Chem. 269(33):20807-20810 (1994). Galectins are members of a family of .beta.-galactoside-binding lectins with related amino acid sequences (For review see, Barondes et al., Cell 76:597-598 (1994); Barondes et al., J. Biol. Chem. 269(33):20807-20810 (August 1994)). Galectin 1 (aka. L-14-1, L-14, RL-14.5, galaptin, MGBP, GBP, BHL, CHA, HBP, HPL, HLBP 14, rIML-1) is a homodimer with a subunit molecular mass of 14,500 which is abundant in smooth and skeletal muscle, and is present in many other cell types (Couraud et al., J. Biol. Chem. 264:1310-1316 (1989)). Galectin 2 was originally found in hepatoma and is a homodimer with a subunit molecular weight of 14,650 (Gitt et al., J. Biol. Chem. 267:10601-10606 (1992)). Galectin 3 (aka. Mac-2, EPB, CBP-35, CBP-30, and L-29) is abundant in activated macrophages and epithelial cells and is a monomer with an apparent molecular mass between 26,320 and 30,300 (Cherayil et al., Proc. Natl. Acad. Sci. USA 87:7324-7326 (1990)). Galectin 4 has a molecular mass of 36,300 and contains two carbohydrate-binding domains within a single polypeptide chain (Oda et al., J. Biol. Chem. 268:5929-5939 (1993)). Galectins 5 and 6 are mentioned in Barondes et al., Cell 76:597-598 (1994). Human galectin 7 has a molecular mass of 15,073 and is found mainly in stratified squamous epithelium (Madsen et al., J. Biol. Chem. 270(11):5823-5829 (1995)).
Animal lectins, in general, often function in modulating cell-cell and cell-matrix interactions. Galectin 1 has been shown to either promote or inhibit cell adhesion depending upon the cell type in which it is present. Galectin 1 inhibits cell-matrix interactions in skeletal muscle (Cooper et al., J. Cell Biol. 115:1437-1448 (1991)). In other cell types, galectin 1 promotes cell-matrix adhesion possibly by cross-linking cell surface and substrate glycoconjugates (Zhou et al., Arch. Biochem. Biophys. 300:6-17 (1993); Skrincosky et al., Cancer Res. 53:2667-2675 (1993)).
Galectin 1 also participates in regulating cell proliferation (Wells et al., Cell 64:91-97 (1991)) and some immune functions (Offner et al., J. Neuroimmunol. 28:177-184 (1990)). Galectin 1 has been shown to regulate the immune response by mediating apoptosis of T cells (Perillo et al., Nature 378:736-739 (1995)).
Galectin 3 promotes the growth of cells cultured under restrictive culture conditions (Yang et al., Proc. Natl. Acad. Sci. USA 93:6737-6742 (June 1996)). Galectin 3 expression in cells confers resistance to apoptosis which indicates that Galectin 3 could be a cell death suppressor which interferes in a common pathway of apoptosis. Id.
Accordingly, there is a need in the art for the identification of novel galectins which can serve as useful tools in the development of therapeutics and diagnostics for regulating immune response.